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Background The feasibility and efficacy of radiation therapy (RT) for central non-small cell lung cancer (NSCLC) remain controversial owing to the increased risk of severe adverse events (AEs), including pneumonia, perforation of mediastinal organs (esophagus and trachea), and bleeding. Carbon-ion radiation therapy (CIRT) is an effective RT modality owing to its steep dose distribution and high biological efficacy. We retrospectively analyzed the clinical course of central NSCLC treated using CIRT. Methods Thirty patients who received CIRT with 68.4 Gy (RBE) in 12 fractions for pathologically proven central NSCLC between 2006 and 2018 were reviewed. The clinical stage was re-evaluated according to the UICC 8th edition, and adverse events were evaluated using CTCAE ver.5.0. The Kaplan–Meier method was used to evaluate overall survival (OS), disease-specific survival (DSS), and local control (LC). Results The median age was 75 years (range 55–85). All patients had concomitant chronic obstructive pulmonary disease (COPD), and 20 (67%) were regarded as inoperable. At a median follow-up of 63 months in surviving patients, 14 patients died, but no treatment-related deaths were observed. The 3-year OS, DSS, and LC rates were 72.4, 75.8, and 88.7%, respectively. Two patients experienced grade 3 pneumonitis, representing 6.7% of the cohort, but no grade ≥ 3 AEs involving the mediastinal organs occurred. Conclusions CIRT using our dose fractionation is feasible and effective for central NSCLC and may be a secure treatment option for patients with central NSCLC who are unmet for other curative treatments.

Highlights • A total of 88 patients experienced light flashes among 416 who received photon radiotherapy and 205 who received proton beam therapy in our prospective study. • The frequency of light flashes during radiotherapy was associated with the retina dose and younger age, and were commonly blue or white light for brain or head and neck irradiation. • Light flashes were seen by only 35/524 patients (6.7%) without retinal irradiation, but by 13/33 (39.4%) and 41/64 (64.1%) with retinal maximum isodose lines of 10–50% and 60–100%, respectively. • Totals of 52, 15, 15, 9, 16 and 8 patients sensed light of blue, purple, yellow, red, white and other colors, respectively., Background Patients who receive radiation therapy sometimes complain of a light flash during irradiation. The details of the characteristics of this light have not been described. Purpose To evaluate light flashes during photon and proton radiotherapy. Methods and Materials A prospective observational study was performed in all adult patients (≥20 years old) who received photon and proton therapy at two centers between January 2019 and August 2020, except for patients who could not communicate and those with visual abnormality. Evaluations were obtained for the presence or absence of light flashes, light darkness (7 levels), light intensity (5 levels), frequency, light movement, light flashing, and time seeing the light, using a weekly checklist. Results A total of 650 courses were examined for 621 patients, of whom 416 received photon radiotherapy and 205 received proton beam therapy. The checklist indicated that 88 patients (16.1%) sensed light during photon or proton radiotherapy. In multivariate logistic regression analysis, the factors that were significantly associated with a light flash were a higher retina dose and younger age (p

Highlights • Proton beam therapy is likely to be safe for liver hemangiomas because, in our experience. • Proton beam therapy achieves good local control for liver hemangiomas without causing severe hepatic damage. • Proton beam therapy expected to minimize the risk of late adverse events., Background Hepatic hemangiomas are benign tumors with a favorable prognosis, but giant hepatic hemangiomas can cause abdominal symptoms and are indicated for treatment. Most cases are treated with surgery, but radiotherapy has also been used. However, to date, there have been no reports of proton beam therapy for a hepatic hemangioma. Case presentation A 46-year-old woman had a tumor of 80 × 80 mm in the left medial lobe of the liver, which was diagnosed as a giant hemangioma based on the contrast pattern. Therapy was required for a giant hepatic hemangioma with symptoms, but the patient refused blood transfusion due to religious reasons, which made surgical resection difficult. Therefore, she was referred to our hospital for proton beam therapy. At her first visit, liver function was Child-Pugh A (5 points) and there was no elevation of tumor markers. Proton beam therapy of 28.6 Gy (RBE) given in 13 fractions was performed without interruption. The only observed acute radiation toxicity was Grade 1 dermatitis. One year after proton beam therapy, the hemangioma had significantly decreased, and a complete response has been maintained for 15 years based on ultrasound and MRI. Conclusion This case is the first reported use of proton beam therapy for a hepatic hemangioma. The outcome suggests that this treatment may be effective for a giant liver hemangioma.

To investigate the outcomes of elderly patients with cT1-3N0M0 non-small cell lung cancer (NSCLC) undergoing proton beam therapy (PBT).Between 2009 and 2019, 110 patients receiving hypofractionated PBT for cT1-3N0M0 NSCLC were retrospectively reviewed.The median follow-up was 36.5 months (range=4.9-131.0 months). In the elderly group (80 years or older), the 3-year overall survival and progression-free survival rates were 79.8% and 73.9%, respectively, and the corresponding rates in the younger group were 80.5% and 61.2%, respectively. Grade 3 radiation pneumonitis (RP) was observed in 4.4% patients in the young group, whereas no grade 3 RP was observed in the elderly group. Age was not a risk factor for symptomatic RP. There were no significant differences in the survival and adverse events between the elderly and younger groups.PBT may be a reasonable approach for treating lung cancer in elderly patients with T1-3N0M0 NSCLC.

Patients often report a sense of smell during radiation therapy (RT), but the details of these events are not well understood. The purpose of the study was to evaluate events of smell during photon RT and proton beam therapy (PBT).The subjects were all adult patients (≥20 years old) treated with photon RT or PBT at two centers from January 2019 to August 2020, with the exclusion of those with communication difficulties or olfactory abnormality. The presence of smell, odor type, intensity (five levels), and time period was examined prospectively using a weekly checklist.A total of 649 courses were examined in 620 patients who received photon RT (n=415) or PBT (n=205). A smell during the procedure was sensed by 51 patients (8.2%). In multivariate logistic regression analysis, nasal cavity dose (p=0.002), age (p0.001), and photon RT (p=0.018) were identified as significant factors associated with a sense of smell. Smell occurred in only 23/515 patients (4.5%) in whom the nasal cavity was not irradiated, but in 4/19 (21.1%) and 24/86 (27.9%) with nasal cavity maximum isodose lines of 10%-50% and 60%-100%, respectively. Patients who received photon RT sensed a smell (43/415; 10.4%) more frequently than those treated with PBT (8/205; 3.9%). Of the 51 patients who sensed a smell, 32 (63%) reported a burnt smell, eight (16%) a chemical smell, two (4%) a sour smell, and nine another smell (copier machine, sweet, garbage, etc.).The sense of a smell appears to be common during RT and this sensation is significantly associated with the nasal cavity dose, younger age, and photon RT.

Background: Langerhans cell histiocytosis (LCH) is a rare disease, especially in adults. It is often associated with non-fatal bone and skin lesions and has relatively good radiosensitivity. In contrast, brain and lymph node metastases from LCH lesions are considered to be less sensitive to radiotherapy. Case Report: At our institution, 30 Gy radiotherapy was used to treat bone lesions with dural invasion in a patient with adult-onset LCH. The patient was treated with chemotherapy and radiotherapy for 21 years since the initial diagnosis. After radiotherapy, the tumor shrank rapidly, and a complete response was achieved 1 year after treatment. The patient survived without local recurrence. Conclusion: Here, we report the details of this case, along with a review of the literature. We suggest that even with invasion of the tissues around the bone lesions in LCH, local recurrence can be prevented by middle radiation doses.

We assessed the development of lymphopenia during concurrent chemoradiotherapy (CRT) using X-ray versus proton beams and the impact on survival in patients with esophageal cancer. Among patients with esophageal cancer who were administered concurrent CRT with a curative intent at our institute from 2014 to 2018, 69 (15 receiving X-ray radiotherapy (XRT) and 54 receiving proton beam therapy [PBT]) who underwent weekly blood testing during treatment were enrolled. The absolute lymphocyte counts (ALC) at 1, 5 and 6 weeks were significantly higher in the patients who received PBT than in those who received XRT (p = 0.002, p = 0.006 and p = 0.009, respectively), and a similar trend in the neutrophil-to-lymphocyte ratio (NLR) was observed (p = 0.003 at 5 weeks). The 2-year overall survival (OS) and progression-free survival (PFS) rates tended to be higher in the patients who maintained an ALC ≥200 compared with those who did not (p = 0.083 and p = 0.053, respectively), and similar trends were observed in the NLR (p = 0.061 and p = 0.038, respectively). Dose–volume analysis revealed significant correlations between volumes of the thoracic bones irradiated by 5–50 Gy and minimum ALCs and maximum NLR. These findings suggested that PBT prevented the development of lymphopenia during CRT by reducing the irradiated volume of the thoracic bone, and the maintained lymphocyte count is possibly one of the early predictors for survival in patients with esophageal cancer.

Although prostate cancer control using radiotherapy is dose‐dependent, dose–volume effects on late toxicities in organs at risk, such as the rectum and bladder, have been observed. Both protons and carbon ions offer advantageous physical properties for radiotherapy, and create favorable dose distributions using fewer portals compared with photon‐based radiotherapy. Thus, particle beam therapy using protons and carbon ions theoretically seems suitable for dose escalation and reduced risk of toxicity. However, it is difficult to evaluate the superiority of particle beam radiotherapy over photon beam radiotherapy for prostate cancer, as no clinical trials have directly compared the outcomes between the two types of therapy due to the limited number of facilities using particle beam therapy. The Japanese Society for Radiation Oncology organized a joint effort among research groups to establish standardized treatment policies and indications for particle beam therapy according to disease, and multicenter prospective studies have been planned for several common cancers. Clinical trials of proton beam therapy for intermediate‐risk prostate cancer and carbon‐ion therapy for high‐risk prostate cancer have already begun. As particle beam therapy for prostate cancer is covered by the Japanese national health insurance system as of April 2018, and the number of facilities practicing particle beam therapy has increased recently, the number of prostate cancer patients treated with particle beam therapy in Japan is expected to increase drastically. Here, we review the results from studies of particle beam therapy for prostate cancer and discuss future developments in this field.

HCC may recur following surgery or radiofrequency ablation. Proton beam therapy (PBT) is a type of radiotherapy that achieves excellent local control of HCC without severe toxicity. The present study reported the long-term outcome of 3 HCC patients who each received 4 repeat courses of PBT. All patients had a hepatitis B or C viral infection. A total of 14 lesions were treated using a curative PBT protocol and irradiated liver volumes in each treatment were 7-50% of the total liver volume. Liver function in all cases was considerably preserved until the last follow-up and patient survival was 51-107 months from the first PBT with no local recurrence observed in the 14 lesions. The presented cases indicated that repeated PBT is an effective treatment option for recurrent HCC due to reduced liver damage and superior local treatment compared with other treatment options such as transarterial chemoembolization.

Background/aim Curing local recurrence of rectal cancer (LRRC) is difficult with conventional photon radiotherapy. Proton beam therapy (PBT) on the other hand, has unique physical characteristics that permit higher doses to LRRC while minimizing side effects on surrounding organs. However, the efficacy of PBT on controlling rectal cancer recurrence has not yet been reported. This study aimed to evaluate clinical outcomes and toxicities of PBT for LRRC. Patients and methods Clinical outcomes were retrospectively evaluated for 12 patients with 13 total lesions that had received PBT for LRRC at our institute. Results The median follow-up period from the initiation of PBT was 35.6 months. The 3-year local control, progression-free survival and overall survival rates were 80.2%, 10.4% and 73.8%, respectively. Median survival time was 67.1 months. There were no severe acute or late adverse events. Conclusion PBT could be a safe and effective treatment method for LRRC.

To evaluate the feasibility and efficacy of deep regional hyperthermia with the use of mobile insulator sheets in a capacitively coupled heating device.The heat was applied using an 8-MHz radiofrequency-capacitive device. The insulator sheet was inserted between the regular bolus and cooled overlay bolus in each of upper and lower side of the electrode. Several settings using the insulator sheets were investigated in an experimental study using an agar phantom to evaluate the temperature distributions. The specific absorption rate (SAR) distributions in several organs were also computed for the three-dimensional patient model. In a clinical prospective study, a total of five heating sessions were scheduled for the pelvic tumours, to assess the thermal parameters. The conventional setting was used during the first, third and fifth treatment sessions, and insulator sheets were used during the second and fourth treatment sessions.In the phantom study, the higher heating area improved towards the centre when the mobile insulator sheets were used. The subcutaneous fat/target ratios for the averaged SARs in the setting with the mobile insulator (median, 2.5) were significantly improved compared with those in the conventional setting (median, 3.4). In the clinical study, the thermal dose parameters of CEM43°CT90 in the sessions with the mobile insulator sheets (median, 1.9 min) were significantly better than those in the sessions using a conventional setting (median, 1.0 min).Our novel heating method using mobile insulator sheets was thus found to improve the thermal dose parameters. Further investigations are expected.

Proton beam therapy (PBT) is a curative treatment for hepatocellular carcinoma (HCC), because it can preserve liver function due to dose targeting via the Bragg peak. However, the degree of direct liver damage by PBT is unclear. In this study, we retrospectively analyzed liver/biliary enzymes and total bilirubin (T-Bil) as markers of direct liver damage during and early after PBT in 300 patients. The levels of these enzymes and bilirubin were almost stable throughout the treatment period. In patients with normal pretreatment levels, aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), and T-Bil were abnormally elevated in only 2 (1.2%), 1 (0.4%), 0, 2 (1.2%), and 8 (3.5%) patients, respectively, and in 8 of these 13 patients (61.5%) the elevations were temporary. In patients with abnormal pretreatment levels, the levels tended to decrease during PBT. GGT and T-Bil were elevated by 1.62 and 1.57 times in patients who received 66 Gy (RBE) in 10 fractions and 74 Gy (RBE) in 37 fractions, respectively, but again these changes were temporary. These results suggest that direct damage to normal liver caused by PBT is minimal, even if a patient has abnormal pretreatment enzyme levels.

Background: Androgen deprivation therapy (ADT) combined with radiation therapy benefits intermediate- and high-risk prostate cancer (PC) patients. The optimal ADT duration in combination with high-dose proton beam therapy (PBT) remains unknown. Methods: Intermediate- and high-risk PC patients treated with PBT combined with ADT for various durations were analyzed retrospectively. To assess the relationship between ADT and biochemical relapse-free (bRF) rate, Cox proportional hazards models including T stage, prostate specific antigen (PSA) level, Gleason score (GS), and total radiation dose were used. Results: In the intermediate-risk PC patients (n = 520), ADT use improved bRF (HR 0.49, 95% CI 0.26&ndash, 0.93, p = 0.029), especially in those with multiple intermediate-risk factors (T2b&ndash, 2c, PSA 10&ndash, 20 ng/mL, and GS 7). In the high-risk PC patients (n = 555), a longer ADT duration (&gt, 6 months) conferred a benefit for bRF (HR 0.54, 95% CI 0.32&ndash, 0.90, p = 0.018), which was most apparent in patients with multiple high-risk factors (T3a&ndash, 4, PSA &gt, 20 ng/mL, and GS &ge, 8) treated with ADT for &ge, 21 months. Conclusions: Short-term (&le, 6 months) ADT is beneficial for intermediate-risk PC patients, but likely unnecessary for those with a single risk factor, whereas ADT for &gt, 6 months is necessary for high-risk PC patients and ADT for &ge, 21 months might be optimal for those with multiple risk factors in combination of high-dose PBT.